KRN5500 in Treating Patients With Solid Tumors

NCT00017238 | Completed Phase 1

• 3 other identifiers: NCI-2012-0313200-102U01CA062490
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I trial to study the effectiveness of KRN5500 in treating patients who have solid tumors. Drugs used in chemotherapy, such as KRN5500, work in different ways to stop cancer cells from dividing so they stop growing or die

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (4)

• Maximally tolerated dose (MTD) and dose limiting toxicities (DLTs) of KRN5500, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0

  Up to 21 days

• Grade 2 or greater toxic effects, based on the NCI CTC v2.0

  Up to 1 month after last course of study treatment

• Plasma concentration-time levels of KRN5500 as determined by reversed-phase high-performance liquid chromatography with electrospray ionization mass spectrometric detection

  Analyzed by noncompartmental methods and/or nonlinear least squares regression using WinNonlin (Scientific Consulting, Inc.).

  Up to 21 days

• Response to KRN5500 by fluorothymidine-positron emission tomography (FLT-PET) scanning at the MTD in patients with measurable disease

  Up to 5 years

Secondary Outcomes (3)

• Antitumor activity

  Up to 5 years

• Pharmacodynamic relationships for the pharmacological effect of the drug upon surrogate markers of activity and host toxicity

  Up to 21 days

• Comparison among the toxicity profiles between the 1 hr i.v. infusion and 72 hr continuous i.v. infusion administration schedules

  Up to 1 month after last course of study treatment

Study Arms (1)

Treatment (KRN5500)

EXPERIMENTAL

Patients receive KRN5500 IV over 24-72 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-3 patients receive KRN5500 at the starting dose over escalating infusion durations. After the longest duration of infusion time is safely reached, cohorts of 3-6 patients receive escalating doses of KRN5500 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with KRN5500 at the recommended phase II dose.

Drug: KRN5500; Other: pharmacological study

Interventions

KRN5500 DRUG

Given IV

Treatment (KRN5500)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (KRN5500)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic or inoperable malignancy, other than leukemia or a primary CNS tumor, for which there is no known curative or survival prolonging palliative therapy, or all such therapies have failed
• Life expectancy \>= 2 months
• ECOG performance status =\< 2
• WBC \>= 3,000/mm\^3
• ANC \>= 1,500/mm\^3
• Platelets \>= 100,000/mm\^3
• SGOT ≤ 2.5-times the upper limit of normal (ULN)
• SGPT ≤ 2.5-times the ULN
• Total bilirubin ≤ 1.5 mg/dl
• Serum creatinine ≤ 1.5 mg/dl
• ECG showing no evidence of acute ischemia or serious conduction abnormality
• \>= 2 weeks since major surgery
• \>= 3 weeks since chemotherapy or radiation therapy, except for nitrosoureas and mitomycin-C, in which case the interval shall be 6 weeks
• Women of childbearing potential must not be pregnant or lactating; all women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of β-HCG) within 72 hr prior to receiving the study medication; KRN5500 has antiproliferative effects which may be harmful to the developing fetus or nursing infant
• Fertile males and females must use adequate contraception

You may not qualify if:

• A serious uncontrolled medical disorder or active infection that would impair the ability of the patient to receive study treatment
• Uncontrolled or significant pulmonary or cardiovascular disease, including a recent (6 months or less) myocardial infarction, any significant degree of congestive heart failure with or without medical treatment, any history of clinically significant atrial or ventricular arrhythmias, any history of second or third degree heart block, or prolonged QTc interval (greater than 450 ms) on electrocardiogram
• Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirement for steroids, or clinical symptoms related to brain metastases
• A psychiatric illness that precludes the ability to provide informed consent

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

KRN 5500

Study Officials

• Joseph Eder

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2001
• First Posted: January 27, 2003
• Study Start: February 1, 2002
• Primary Completion: November 1, 2008
• Last Updated: January 11, 2013

Record last verified: 2013-01

Locations

US (1)